Abstract

The solid-state and solution conformations of the model peptide Boc-Aib-Pro-Pro-NHMe have been studied by X-ray diffraction and NMR. The peptide adopts a poly(pro1ine 11) conformation in the solid state. Two molecules are observed in the asymmetric unit differing in the geometry (cisltrans) of the urethane group. The molecules are held together in the crystal by a complex network of hydrogen bonds involving three molecules of water, which cocrystallize. Dissolution of single crystals at low temperature (\sim 233 K) permits NMR observation of the solid-state conformer. In solution, the peptide undergoes a trans-cis isomerization of the Pro-Pro bond. Low- temperature NMR measurements allow the detection of three conformational states of the Pro-Pro segment. Both cis’ and trans’ rotational isomers about the $C^\alpha -CO$ $(\psi)$ bond of Pro-3 are detectable at low temperatures. Theoretical calculations suggest an appreciable activation barrier to $\psi$ rotation. Temperature and solvent dependence of NH chemical shifts provide evidence for an intramolecular hydrogen bond, involving the NHMe group in the cis Pro-Pro conformer. Energy calculations suggest the possibility of a type VI $\beta$-turn conformation stabilized by a 4 $\rightarrow$ 1 hydrogen bond between the Aib-1 CO and NHMe groups.